L25-26: Protein and AA Metabolism I-II Flashcards Preview

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Flashcards in L25-26: Protein and AA Metabolism I-II Deck (60):

Describe protein digestion in the digestive tract

- Acidic pH of stomach denatures proteins - Pepsinogen is secreted by the stomach - It autoinhibits it’s active site, becomes altered in acidic environment and cleaves itself into pepsin - Pepsin’s active site contains aspartic acid residues. - It is a endopeptidase and cleaves internal peptide bonds, prefers bonds formed between AA groups of aromatic and hydrophobic amino acids - Chyme enters duodenum, stimulates release of secretin and CCK by intestinal mucosa - Secretin: stimulates acinar cells in pancreas = alkaline fluid released (bicarb rich), which neutralizes chym - CCK: stimulates release of bile and release of pancreatic digestive zymogens (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases) - Enteropeptidase present on wall of intestinal mucosa cleaves trypsinogen to trypsin - Trypsin cleaves remaining pancreatic zymogens into active forms (chymotrypsin, elastase, carboxypeptidases)


Function of pepsin

- Endopeptidase that prefers cleaving bonds formed bw aromatic and hydrophobic AA groups


List of pancreatic digestive enzymes

- trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases


Function of trypsinogen

- Activating pancreatic digestive zymogens and also acting as a protease


Function of secretin

- neutralizes chyme for the purpose of allowing function of pancreatic digestive enzymes


Function of CCK

- stimulates release of digestive enzymes from pancreas - stimulates release of bile from GB


Where are secretin and CCK released from? What stimulates their release?

- intestinal mucosa cells - stimulated by chyme


Function of enteropeptidase. Where is it found?

- found on intestinal mucosa - cleaves trypsinogen to trypsin


What is the ratio of peptides to free amino acids that pancreatic proteases and peptidases?

- 60% peptides : 40% free amino acids


Describe transport of peptides and amino acids across the intestinal mucosa

- Pancreatic proteases and peptidases generate 60:40 ratio of peptides:free amino acids - Endopeptidases and aminopeptidases on luminal surface of epithelial of small intestine generate free AAs or di/tri peptides, which are absorbed via several transport systems - Specific AA transports require energy input often via secondary active transporters (coupled to sodium gradients) - Di/tri-peptide transport require energy input via proton gradients - Peptidases in epithelial cells hydrolyze di/tri peptides to free AAs - Free AAs exit across basal membrane into circulation via facilitated diffusion


Difference between AA and CHO transport across intestinal mucosa.

- CHO need to be in monosaccharide form in order to pass via specific receptors - AAs can be in free AA or di/tri peptide form in order to pass via specific receptors


What is acute pancreatitis? Symptoms? Causes? Triggers? Treatment?

- Inflammatory disease of pancreas caused by premature activation of pancreatic digestive zymogens - Symptoms = abdominal pain, vomiting - Causes = pancreatic necrosis - Triggers = alcohol, infections, gallstones - Treatment = supportive via analgesics, fasting, elemental jejunal tube or TPN


What is Hartnup disease? Symptoms? Treatment?

- Rare genetic disorder affecting transporter of large, neutral amino acid resulting in no absorption of these amino acids across intestinal epithelial cells, also in prox tubule of kidney causing elimination issue - Symptoms? Similar to pellagra, which is niacin deficiency – 4 D’s – diarrhea, dermatitis, dementia, death. - Treatment? Dietary supplementation with niacin


What is celiac disease? Cause? Result? Symptoms? Treatment?

- Inappropriate immune respone to alpha-gliadin, which is a glycoprotein found in wheat and other grains - Result? Reduction of absorptive area of small intestine, results in malabsorption - Symptoms? Abdominal cramps, bloating and malabsorptive symptoms - Treatment? Avoidance of alpha-gliadin containing foods


What is meant by term ‘amino acid pool’?

- Sum of intracellular and extracellular free AAs – ie. those not incorporated into proteins


What is meant by term nitrogen balance?

- Steady state condition whereby nitrogen content of diet equals excretion of nitrogenous waste products.


What is meant by term positive nitrogen balance? What does this lead to?

- Incorporation of dietary AAs into proteins exceeds protein breakdown - Leads to periods of growth/new protein synthesis


What is meant by term negative nitrogen balance? What does this lead to?

- Insufficient dietary amino acids to offset degradation of endogenous protein - Leads to wasting disease or starvation


Daily protein requirement?

- 50-100 grams


What is meant by term essential AAs. List them. Special case

- AAs that cannot be synthesized - Pvt Tim Hall = mnemonic - Phe, Val, Thr, Try, Iso, Met, His, Arg, Leu, Lyc - Special case = Arg – can be synthesized, not sufficiently to keep up with needs


Can we synthesize arginine?

- Yes, but not enough to keep up with needs during periods of growth, therefore making it essential AA in infants, but not adults


Is arginine an essential AA? When?

- In infants, not adults.


Which AA promotes would healing especially in pressure ulcer patients?

- Arginine


What foods are complete proteins?

- Meat, fish, eggs, poultry, soy beans


What AAs are made from: alpha-ketoglutarate and oxaloacetate?

- Asp, Asn, Arg, Glu, Gln, Pro


From what are Asp, Asn, Arg, Glu, Gln and Pro made from?

- alpha-ketoglutarate and oxaloacetate


What AAs are made from pyruvate and 3-PG?

- Ala, Ser


From what are Ala and Ser made from?

- Pyruvate and 3-PG


What are Tyr and Cys made from?

- From Phe and Met, which are both essential AAs


What is Ser a precursor to?

- Glycine


What is Gly made from?

- From serine, which is made from 3-PG


Describe the general reaction catalyzed by aminotransferases. What is the common alpha-ketoacid and alpha-aminoacid pair used in some reactions?

- Common alpha-ketoacid and alpha-aminoacid pair: alpha-ketoglutarate (acts acid amino group acceptor) and glutamate (acts as amino group donor)



Common alpha-ketoacid/aminoacid pairs in reactions with alpha-ketoglutarate/glutamate?

- pyruvate/alanine - oxaloacetate/aspartate


Cofactor requirement(s) for aminotransferases.

- Vitamin B6 (pyridoxal 5’-phosphate)


Synthesis of alanine


What is ALT?

- alanine aminotransferase - synthesizes alanine and alpha-ketoglutarate from pyruvate and glutamate


Synthesis of aspartate


Main source of glutamate is the diet. How else is it synthesized in the body?

- Transamination via aminotransferase enzyme (ALT / AST) - Deamidation of glutamine via glutaminase



What reaction does glutamate dehydrogenase catalyze in vivo?

- glutamate + NAD+ + H2O = alpha-ketoglutarate + NADH + NH4+


Synthesis of glutamine


What molecule is the temporary ammonium ion carrier in the body?

- glutamine


Describe how ammonium ions are transported and excreted within the blood

- Glutamine produced in peripheral tissues enters the bloodstream and is absorbed by the kidneys, liver and gut - Amide group is hydrolyzed by glutaminase and produces glutamate and ammonium ion - Kidney excretes NH4+ directly and liver produces urea in urea cycle. Glutamine is nutrient in gut, ammonium enters hepatic portal and metabolized by liver


How is gluconeogenesis in liver connected with muscle glycolysis?

- Glucose enters glycolysis with pyruvate as end product - Pyruvate is converted into alanine via ALT and sent into bloodstream - Alanine is taken up by liver and converted back into pyruvate by ALT - Pyruvate is converted into glucose via gluconeogenesis


What is the clinical significance of ALT and AST?

- AST found at highest levels in liver, but also in other tissues including cardiac muscle - ALT abundant in liver - Both are normally low in serum - When tissues are damaged, these enzymes are released into the serum - Elevation of AST indicates liver disease, but also acute MI, kidney damage, pancreatitis etc. - Elevation of ALT is more specific indicator of liver damage


Which aminotransferase enzyme is the more specific indicator of liver damage?



Synthesis of serine


Synthesis of glycine

- PLP = active form of B6



What is the main dietary source of glycine?

- collagen


Asparagine synthesis


What is THF? What is its function? Where is it derived from?

- THF = tetrahydrofolate - Serves as a carrier of one carbon groups - Derived from folate, vitamin B9, which is found in foliage, green leafy veg, liver, eggs and beans


Most oxidized form of THF and most reduced form of THF? Which form accumulates within the body? In context of THF, what is the one carbon pool and what are the major contributors? Which THF form accumulates in body?

- oxidized form: N10-formyl THF - reduced form: N5-methyl THF - THF can carry and move single carbon molecules around the body. - Major one carbon pool source = serine via 3-PG - Minor sources = formaldehyde (from methanol), formate (from tryptophan), histidine - Accumulated THF form: N5-methyl THF


Synthesis of cysteine

- s-adenosylhomocysteine is acted on by adenosylhomocysteinase, which generates adenosine and homocysteine - cystathionine beta-synthase and cystathionase are both B6 requiring enzymes



Describe homocystinuria. Causes? Symptoms? Treatment?

- Grossly evelated homocysteine (plus other metabolites of this) accumulat in body and are seen in urine - Most commonly due to cystathionine beta-synthase mutation - Symptoms: dislocation of optic lens, osteoporosis, lengthening and thinning of long bones, thromboembolism, intellectual disability - Treatment: low methionine diet with cysteine supplements, pyridoxine or betaine supplements


Synthesis of tyrosine


What AA is the precursor to tyrosine? Is this reaction reversible – that is, can tyrosine be used to make the precursor AA?

- Not a reversible reaction


What two molecules are carriers of methyl groups?

- SAM and THF


What are the products, substrates, cofactors of phenylalanine hydroxylase?

- substrates: o2, THBtn, phenylalanine - products: tyrosine, H2o and DHBtn - cofactors: DHBtn reductase, which requires NADH


In which organ is phenylalanine hydroxylase primarily located?

- Liver


What is phenylketonuria. Causes? Pathology? Symptoms? Treatment? Why avoid aspartame if phenylketonuric?

- Mutation in phenylalanine hydroxylase (more common) or DHBtn reductase leads to a elevation of phenylpyruvate, phenylalanine and other metabolites. - Pathology: not fully understood, but: accumulation of phenylalanine competitively inhibits the transport of other AAs across the BB barrier, which might interfere with NT synthesis. Also leads to reduced synthesis and increased degradation of myeline. Phe is also a competitive inhibitor of tyrosinase and intereferes with melanin synthesis - Symptoms: intellectual disability, recurrent seizures, hypopigmentation, eczematous skin rashes - Treatment: limiting dietary Phe (not eliminating, as it is essential), supplementation with tyrosine, treatment before child is 3 weeks of age, lifelong monitoring of plasma phenylalanine - Aspartame is a dipeptide of aspartic acid and methylated Phe derivative. Eating will cause formation of phenylalanine


Synthesis of proline